ArticleCell2017
HSP90 Shapes the Consequences of Human Genetic Variation.
Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 136 citations in OpenAlex.
- A conserved post-maturity imbalance between housekeeping and integrative genome activity in aging.GeroScience · 2026Article
- Integrative proteomics defines FANCA as a multifunctional hub linking DNA repair to translation.iScience · 2026Article
- Spliceosome buffers cryptic genetic variation to enforce phenotypic robustness inScience advances · 2026Article
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- These 'master' proteins protect us from deadly mutations - and could inspire new drugs.Nature · 2026Article
- Dominant-negative TP53 mutations potentiated by the HSF1-regulated proteostasis network.Molecular cell · 2026Article
- HSP90 buffers deleterious genetic variations in BRCA1.Molecular cell · 2025Article
- HSP90 as an evolutionary capacitor drives adaptive eye size reduction via atonal.Nature communications · 2025Article
- Review
- HSF1 remodels mitochondrial biogenesis and function in cancer cells via TIMM17A.bioRxiv : the preprint server for biology · 2025Article
- Hsp90: Bringing it all together.Cell stress & chaperones · 2025Review
- Disruption of the moonlighting function of CTF18 in a patient with T-lymphopenia.Frontiers in immunology · 2025Article
- The Hsp90 Molecular Chaperone as a Global Modifier of the Genotype-Phenotype-Fitness Map: An Evolutionary Perspective.Journal of molecular biology · 2024Review
- Selection for robust metabolism in domesticated yeasts is driven by adaptation to Hsp90 stress.Science (New York, N.Y.) · 2024Article
- Tracing genetic diversity captures the molecular basis of misfolding disease.Nature communications · 2024Article
- Protein-folding chaperones predict structure-function relationships and cancer risk in BRCA1 mutation carriers.Cell reports · 2024Article
- Phenotypic heterogeneity in human genetic diseases: ultrasensitivity-mediated threshold effects as a unifying molecular mechanism.Journal of biomedical science · 2023Review
- Identification of genotype-biochemical phenotype correlations associated with fructose 1,6-bisphosphatase deficiency.Communications biology · 2023Article
- Differential Hsp90-dependent gene expression is strain-specific and common among yeast strains.iScience · 2023Article
- Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function. In contrast, the function of less severe mutants was preserved by a dominant increase in HSP90 binding. Reducing HSP90's buffering capacity with inhibitors or febrile temperatures destabilized HSP90-buffered mutants, exacerbating FA-related chemosensitivities. Strikingly, a compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding. These findings provide one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.